This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We successfully synthesized four variations of lead candidate PET compounds, including unlabeled fluorinated and iodinated versions. We determined the relative affinity of the test compounds for human vasopressin and oxytocin receptor. Results indicated that each of the modified versions of lead compound was highly selective for human oxytocin receptor, with binding affinities 500 nM for human vasopressin receptor. Our candidate fluorine-18 ligand was labeled and subjected to tissue harvest studies using rat models. Results for brain penetration were inconclusive and log P values were again found to be in desired range. We opted to perform in vivo PET scans using rat models on our microPET/CT scanner. PET scans on four rats displayed no brain penetration, but significant uptake of ligand appeared in the pituitary gland where oxytocin and vasopressin are stored prior to peripheral release. Our candidate carbon-11 ligand was labeled and investigated in rat model via microPET/CT. Once again the lipophilicity was found to be in desired range, and despite having lowest molecular weight of all candidates, the compound did not display penetration into the brain. We were disappointed in initial results but believe that we have a sound plan to continue and are optimistic that we will succeed in developing a PET ligand. Plan includes trying to permeablize the blood-brain barrier by co-injection mannitol, as well as producing derivatives of other small molecule ligands with smaller molecular weights or there is evidence of penetration of the blood brain barrier.